rs17020983

chr1-207114952-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000715.4(C4BPA):c.329-464C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,116 control chromosomes in the GnomAD database, including 5,311 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (5311 hom., cov: 31)
• Consequence: C4BPA NM_000715.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188

Genes affected

C4BPA (HGNC:1325): (complement component 4 binding protein alpha) This gene encodes a member of a superfamily of proteins composed predominantly of tandemly arrayed short consensus repeats of approximately 60 amino acids. Along with a single, unique beta-chain, seven identical alpha-chains encoded by this gene assemble into the predominant isoform of C4b-binding protein, a multimeric protein that controls activation of the complement cascade through the classical pathway. The genes encoding both alpha and beta chains are located adjacent to each other on human chromosome 1 in the regulator of complement activation gene cluster. Two pseudogenes of this gene are also found in the cluster. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C4BPA	NM_000715.4	c.329-464C>T		intron_variant		ENST00000367070.8
C4BPA	XM_005273251.3	c.329-464C>T		intron_variant
C4BPA	XM_005273252.5	c.329-464C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C4BPA	ENST00000367070.8	c.329-464C>T		intron_variant		1	NM_000715.4	P1
C4BPA	ENST00000421786.5	c.329-464C>T		intron_variant		4
C4BPA	ENST00000424088.1	c.*67+181C>T		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30186 AN: 151998 Hom.: 5300 Cov.: 31

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0604

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.0769

Gnomad OTH AF: 0.186

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.199 AC: 30224 AN: 152116 Hom.: 5311 Cov.: 31 AF XY: 0.196 AC XY: 14540 AN XY: 74360

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.0604

Gnomad4 NFE AF: 0.0769

Gnomad4 OTH AF: 0.184

Alfa AF: 0.106 Hom.: 1393

Bravo AF: 0.215

Asia WGS AF: 0.195 AC: 677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.5
Dann	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17020983; hg19: chr1-207288297;